Differential Mobility Spectrometers (DMS), also referred to as a Field Asymmetric Waveform Ion Mobility Spectrometers (FAIMS) or Field Ion Spectrometers (FIS), typically perform gas-phase ion sample separation and analysis by continuously transmitting ions-of-interest while filtering out unwanted species. In some circumstances, a DMS can be interfaced with a mass spectrometer (MS) to take advantage of the atmospheric pressure, gas-phase, and continuous ion separation capabilities of the DMS and the detection accuracy of the MS. By interfacing a DMS with an MS, numerous areas of sample analysis, including proteomics, peptide/protein conformation, pharmacokinetics, and metabolism analysis have been enhanced. In addition to pharmaceutical and biotech applications, DMS-based analyzers have been used for trace level explosives detection and petroleum monitoring.
A DMS, like an ion mobility spectrometer (IMS), is considered an ion mobility based analyzer because the DMS separates and analyzes ions based on the mobility characteristics of the ions rather than based on the mass-to-charge ratio as in MS. Specifically in DMS, ions within a drift gas can be continuously pulsed or transmitted into a drift tube or gap between two parallel electrodes that generate an asymmetric electric field (S or separation field) therebetween that tends to move the ions in a direction perpendicular to the direction of the drift gas flow (i.e., toward the electrodes). The asymmetric field (S) can be generated by applying an electrical signal(s) to one or more of the electrodes so as to generate an asymmetric waveform, the amplitude of which is referred to as the separation voltage (SV). Typically, the asymmetric field S exhibits a high field duration at one polarity and then a low field duration at an opposite polarity, with the durations of the high field and low field portions set such that the net electrical force on the ions in a direction perpendicular to the direction of the gas flow (i.e., in the direction of the electrodes) over each period is zero during each cycle of the SV. Because a particular ion's mobility through the drift gas during the high and low field portions of the SV can be a function of each particular ion's size, shape, and charge state (and its interactions with the background gas), the various ions' flight paths through the DMS can deviate from the center of the chamber toward the electrodes as the ion drifts therebetween unless the ions' trajectories are corrected by a counterbalancing force. In DMS, this counterbalancing force is typically provided by a DC compensation field (C), in which a DC voltage difference between the electrodes (compensation voltage, CV) can restore a stable trajectory for a subset of the ions, thereby allowing these ions to be transmitted from the DMS. In this manner, the CV can be set to a fixed value corresponding to the optimum transmission of an ion of interest (e.g., based on theoretical calculations or empirical data) such that the ions of interest and other ion species exhibiting a stable trajectory within the differential mobility field (e.g., the field at that SV/CV combination) are transmitted by the DMS, while non-desired, unstable ions are neutralized at the electrodes. Rather than maintain a fixed combination of SV/CV throughout the sample run, conventional DMS systems can be operated by varying the strength of the SV and/or the CV over time (e.g., by scanning the CV to increase its magnitude during a sample run, by providing stepwise increases to CV) so as to iteratively transmit ions of different characteristic mobilities at each particular SV/CV combination.
Because conventional DMS methods and devices only enable a single SV/CV combination to be applied at a given time, known DMS techniques can require more sample runs (e.g., sample injections) to be performed in order to apply the various SV/CV pairs, thereby reducing sample throughput and/or increasing sample consumption. Though conventional DMS devices can alternatively be operated by varying the SV and/or CV over time so as to iteratively transmit ions of different mobilities during a single sample run, such methods can nonetheless result in increased sample consumption, as well as duty cycle loss and/or increased data acquisition times due to the time required to switch the CV value (typically on the order of about 20 ms). Conventional DMS devices could alternatively be operated at sub-optimal conditions so as to ensure transmission of ion species having different characteristic mobilities. By way of example, conventional DMS devices could be operated at a SV/CV pair such that each of two ions of interest are transmitted, with neither being at its theoretical or empirical optimum CV apex corresponding to its maximum transmission. Alternatively, the residence time of the ions within the DMS can be decreased (e.g., by increasing the rate of the drift gas) such that more ions exhibit a stable trajectory at each SV/CV pair due to the decreased residence time in the asymmetric field. Such sub-optimal methods, however, can result in decreased sensitivity, decreased resolution, and/or the increased transmission of undesired ions.
Accordingly, a need exists for improved differential mobility spectrometers and methods of operating the same.